title: Substitution of anti-androgens and tegafur-uracil combination therapy for castration-resistant prostate cancer: results of a multi-center randomized phase II study.
abstract: We conducted this study to determine whether substitution with anti-androgen (SOA) and tegafur-uracil (a pro‑drug of 5-FU) combination therapy is more effective than SOA alone after relapse from initial hormonal therapy. Patients who were histologically confirmed and relapsed after initial hormonal therapy were included. All patients were randomly allocated into two groups: SOA alone (group A) or SOA combined with tegafur-uracil (group B). The mRNA expression of four enzymes, including thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), orotate phospho-ribosyltransferase (OPRT) and thymidine phosphorylase (TP), in prostate cancer cells was analyzed by quantitative reverse-transcription polymerase chain reaction. Fifty-two patients were enrolled in this study. The median age was 77 (range: 47-92) years. The PSA response rate in group B (61.5%) tended to be higher compared to that in group A (34.6%) (p=0.095). Group B (median: 15.9 months) had a significantly longer time to PSA progression (TTP) compared to group A (6.4 months) (p=0.014). In patients with a lower TS expression or a higher OPRT expression, group B demonstrated a higher PSA response rate compared to group A (p=0.019 and p=0.041, respectively). In addition, in the patients with a lower TS expression, group B demonstrated a significantly longer TTP compared to group A (p=0.018). There were no severe adverse events in either treatment group. After relapse from initial hormonal therapy, SOA combined with tegafur-uracil is effective and well tolerated. The TS mRNA expression level may be a predictive factor for this combination therapy.
authors.affiliation: Department of Urology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8503, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Takahashi
authors.forename: Rumi
authors.initials: R
authors.lastname: Kawabata
authors.forename: Akira
authors.initials: A
authors.lastname: Kawano
authors.forename: Yoshihide
authors.initials: Y
authors.lastname: Murakami
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Sutou
authors.forename: Tohru
authors.initials: T
authors.lastname: Inai
authors.forename: Seiji
authors.initials: S
authors.lastname: Akazawa
authors.forename: Takumi
authors.initials: T
authors.lastname: Hamao
authors.forename: Hideki
authors.initials: H
authors.lastname: Hayashi
authors.forename: Tomoya
authors.initials: T
authors.lastname: Fukawa
authors.forename: Masahiko
authors.initials: M
authors.lastname: Takemura
authors.forename: Yasuyo
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Kunihisa
authors.initials: K
authors.lastname: Yamaguchi
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Izaki
authors.forename: Tomoharu
authors.initials: T
authors.lastname: Fukumori
authors.forename: Hiroomi
authors.initials: H
authors.lastname: Kanayama
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000096:biosynthesis; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D009962:Orotate Phosphoribosyltransferase / Q000096:biosynthesis; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis; D005641:Tegafur / Q000008:administration & dosage*; D013939:Thymidine Phosphorylase / Q000096:biosynthesis; D013940:Thymidylate Synthase / Q000096:biosynthesis; D014498:Uracil / Q000008:administration & dosage*
chemical_list: D000726:Androgen Antagonists; D012333:RNA, Messenger; D005641:Tegafur; D014498:Uracil; D042943:Dihydrouracil Dehydrogenase (NADP); D013940:Thymidylate Synthase; D009962:Orotate Phosphoribosyltransferase; D013939:Thymidine Phosphorylase